SCD5 restored expression favors differentiation and epithelialmesenchymal reversion in advanced melanoma

Research output: Contribution to journalArticle

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Abstract

Our previous data supported a role for the Stearoyl-CoA desaturase (SCD5) in protection against malignancy, whereby it appears to functionally modify tumor stroma impairing tumor spread. SCD5 is significantly expressed in primary melanoma, but becomes barely detectable at tumor advanced stages. Looking for the regulatory mechanisms underlying SCD5 reduced expression during melanoma progression, we demonstrated a significantly lower stability of SCD5 protein as well as the direct targeting of SCD5 mRNA by the oncogenic miR-221 & 222 in metastatic cell lines. Moreover, our results indicated the existence of a negative feedback loop between SCD5 and miR-221 & 222, in good agreement with their opposite functions. Also, we showed how SCD5 re-expression and the direct supplementation of its main product oleic acid (OA) can drive advanced melanoma cell lines toward differentiation and reversion of the epithelial-mesenchymal (EMT)-like process, eventually inducing a less malignant phenotype. Indeed, SCD5 re-established the sensitivity to all-trans retinoic acid in A375M metastatic melanoma, associated with increased levels of Tyrosinase, melanin production and reduced proliferation. As evidenced by the correct modulation of some key transcription factors, SCD5 managed by favoring a partial mesenchymal-to-epithelial (MET) transition in in vitro studies. Interestingly, a more complete MET, including E-cadherin re-expression correctly localized at cell membranes, was obtained in in vivo xenograft models, thus indicating the requirement of direct contacts between tumor cells and the surrounding microenvironment as well as the presence of some essential factors for SCD5 complete function.

Original languageEnglish
Pages (from-to)7567-7581
Number of pages15
JournalOncotarget
Volume9
Issue number7
DOIs
Publication statusPublished - Jan 26 2018

Fingerprint

Melanoma
Neoplasms
Stearoyl-CoA Desaturase
Cellular Microenvironment
Cell Line
Epithelial-Mesenchymal Transition
Monophenol Monooxygenase
Protein Stability
Melanins
Cadherins
Oleic Acid
Tretinoin
Heterografts
Transcription Factors
Cell Membrane
Phenotype
Messenger RNA

Keywords

  • Differentiation
  • Melanoma
  • Mesenchymal-to-epithelial transition
  • MiR-221 & 222
  • SCD5

ASJC Scopus subject areas

  • Oncology

Cite this

SCD5 restored expression favors differentiation and epithelialmesenchymal reversion in advanced melanoma. / Puglisi, Rossella; Bellenghi, Maria; Pontecorvi, Giada; Gulino, Alessandro; Petrini, Marina; Felicetti, Federica; Bottero, Lisabianca; Mattia, Gianfranco; Carè, Alessandra.

In: Oncotarget, Vol. 9, No. 7, 26.01.2018, p. 7567-7581.

Research output: Contribution to journalArticle

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